Renal allograft fibrosis is one of the common and severe complications after kidney transplantation, which seriously affects the function and survival rate of renal allograft, and may even lead to organ failure and patient death. At present, the researches on renal allograft fibrosis are highly complicated, including immunity, ischemia-reperfusion injury, infection and drug toxicity, etc. The diagnosis and treatment of renal allograft fibrosis remain extremely challenging. In this article, the latest research progress was reviewed and the causes, novel diagnosis and treatment strategies for renal allograft fibrosis were investigated. By improving diagnostic accuracy and optimizing treatment regimen, it is expected to enhance clinical prognosis of kidney transplant recipients, aiming to provide reference for clinicians to deliver proper management for kidney transplant recipients.

Objective:To investigate the clinical utility of 68Ga-labeled fibroblast activation protein inhibitor (FAPI) PET/CT in the detection of primary and metastatic gastric signet-ring cell carcinoma (GSRCC) and compared the results with those of 18F-FDG PET/CT. Methods:A total of 21 patients (10 males, 11 females, average age 52 years) with primary and metastatic GSRCC who underwent 68Ga-FAPI and 18F-FDG PET/CT at the First Affiliated Hospital of Xiamen University from June 2020 to May 2022 were retrospectively analyzed. Pathological results of surgery and (or) biopsy were used as the " gold standard" for final diagnosis. In cases whose surgery or tissue biopsies were not available, clinical and radiographic follow-up results were used as the reference standards. Wilcoxon signed-rank test was used to compare the SUV max of 18F-FDG and 68Ga-FAPI. McNemar χ2 test was used to compare the detection rate between 18F-FDG and 68Ga-FAPI PET/CT. Results:68Ga-FAPI PET/CT showed higher SUV max than 18F-FDG in primary tumors (5.3(2.4, 15.7) vs 2.4(1.8, 2.5); z=2.31, P=0.021), local recurrences (7.8(6.0, 8.9) vs 2.4(1.9, 3.4); z=2.20, P=0.028), lymph nodes metastases (7.7(4.5, 12.2) vs 2.4(1.9, 3.6); z=6.01, P<0.001) and bone/visceral metastases (6.7(5.3, 11.1) vs 2.4(2.0, 3.4); z=11.36, P<0.001). Regarding diagnostic accuracy, 68Ga-FAPI PET/CT showed higher sensitivities than 18F-FDG for primary tumors (7/9 vs 2/9; χ2=3.20, P=0.063) and local recurrences (7/7 vs 2/7; χ2=3.20, P=0.063). It also demonstrated higher lesion detection rates than 18F-FDG for suspicious lymph node metastases (86%(65/76) vs 32%(24/76); χ2=31.37, P<0.001) and bone/visceral metastases (99%(184/185) vs 39%(73/185); χ2=107.08, P<0.001). Conclusions:68Ga-FAPI PET/CT showed higher tumor uptake and lesion detection rate than 18F-FDG in the primary and metastatic GSRCC. 68Ga-FAPI PET/CT demonstrates good diagnostic performance for tumor detection, staging, and restaging of GSRCC, which is helpful to further guide clinical treatment strategy.

Objective:To develop a tetramer probe targeting fibroblast activation protein (FAP), named 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-4P(FAP inhibitor (FAPI)) 4, evaluate its biodistribution and PET image in FAP-positive-tumor bearing nude mice, and explore its feasibility as a novel radio-regent for treatment of FAP-positive tumor. Methods:FAP tetramer probe was constructed on the FAPI-46 motif with four mini-polyethylene glycol (PEG)(PEG 3) spacers between the four FAPI motifs, denoted as 4P(FAPI) 4. DOTA was used as the chelator for radiolabeling with 68Ga and 177Lu. The FAP binding characteristics were test by in vitro cell competitive binding experiment. Small-animal PET, in vivo biodistribution, and radionuclide targeting therapy were performed in HT-1080-FAP tumor bearing nude mice ( n=39). Independent-sample t test was performed to analyze tumor uptake data, and two-factor repeated measures analysis of variance was utilized to compare tumor volume data in radioactive isotope therapy. Results:Cell experiment showed that FAPI-tetramer and FAPI-monomer had similar half maximal inhibitory concentration values (3.29 and 2.15 nmol/L). 68Ga/ 177Lu radiolabeled FAPI-tetramer had better tumor uptake and retention than FAPI-monomer in small-animal PET and in vivo biodistribution experiment, with the tumor uptake for 177Lu-DOTA-4P(FAPI) 4 and 177Lu-FAPI-46 at 48 h of (18.72±1.32) vs (2.72±1.20) percentage activity of injection dose per gram of tissue (%ID/g) ( t=15.55, P<0.001). 177Lu-DOTA-4P(FAPI) 4 group showed best anti-tumor efficacy compared with 177Lu-FAPI-46 and control group in radionuclide targeting therapy. On the 2nd day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the control group (mean difference 67.19 mm 3, P=0.049); on the 14th day after the start of treatment, the tumor volume in the tetramer treatment group was significantly smaller than that in the monomer treatment group (mean difference 414.33 mm 3, P=0.005). Conclusion:FAPI-tetramer can improve tumor uptake and retention ability compared with FAPI-46, and 177Lu-DOTA-4P(FAPI) 4 can be a promising radio-agent for FAP-positive tumor therapy.

Multiple sclerosis (MS) is regarded as a chronic inflammatory disease that leads to demyelination and eventually to neurodegeneration. Activation of innate immune cells and other inflammatory cells in the brain and spinal cord of people with MS has been well described. However, with the innovation of technology in glial cell research, we have a deep understanding of the mechanisms of glial cells connecting inflammation and neurodegeneration in MS. In this review, we focus on the role of glial cells, including microglia, astrocytes, and oligodendrocytes, in the pathogenesis of MS. We mainly focus on the connection between glial cells and immune cells in the process of axonal damage and demyelinating neuron loss.
Humans ; Multiple Sclerosis ; Neuroglia ; Inflammation/pathology* ; Brain/pathology* ; Spinal Cord/pathology*

Objective:To evaluate the clinical efficacy of Jianpi Bushen Zhixie Recipe combined with conventional western medicine therapy in the treatment of diabetic diarrhea patients with spleen and kidney yang-deficiency syndrome.Methods:According to the random number table method, 62 patients with diabetic diarrhea with spleen and kidney yang-deficiency syndrome from June 2019 to June 2021 in Shunyi Hospital of Beijing Traditional Chinese Medicine Hospital, who met the inclusion criteria, were divided into two groups, with 31 in each group. The control group was treated with standardized hypoglycemic and mecobalamin treatment, while the treatment group was treated with Jianpi Bushen Zhixie Recipe on the basis of the control group. Both groups were treated for 2 weeks and followed up for 2 weeks. Before and after treatment, TCM syndrome scores and Bristol Stool Form Scale (BSFS) scores were performed before and after treatment. The Health Related Quality of Life Scale (SF-36) was used to evaluate the quality of life of patients. The number of bowel movements and adverse reactions during treatment were recorded before and after treatment, and followed up for 2 weeks to observe the disease recurrence rate.Results:The total effective rate was 93.55% (29/31) in the treatment group and 74.19% (23/31) in the control group, with a statistically significant difference between both groups ( χ2=5.44, P=0.020). After treatment, the number of bowel movements in the treatment group [(1.02±0.23) times/d vs. (2.35±0.45) times/d, t=14.65] was significantly lower than that of the control group ( P<0.01); the BSFS scores (1.93±0.43 vs. 3.23±0.43, t=11.87) and TCM syndrome score (0.93±0.25 vs. 1.95±0.36, t=12.96) in the treatment group were significantly lower than those in the control group ( P<0.01); the SF-36 score (92.32±2.99 vs. 86.23±3.12, t=7.85) in the treatment group was significantly higher than that of the control group ( P<0.01). No gastrointestinal adverse events were found in both groups during treatment. During the follow-up period, there were 4 cases (4/23) of recurrence in the control group after treatment, and no recurrence in the treatment group. There was a statistically significant difference in the recurrence rate between the two groups ( χ2=4.28, P=0.039). Conclusion:The Jianpi Bushen Zhixie Recipe combined with conventional western medicine can improve symptoms and quality of life of patients with diabetic diarrhea with spleen and kidney yang-deficiency syndrome, reduce adverse reactions and recurrence rate.

Background/Aims: Epstein-Barr virus-associated gastric cancers (EBVaGCs) have unique molecular and clinicopathological characteristics. The cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is recently recognized as the critical innate immunity against pathogens and tumors. STING is also a master regulator in the cancer-immunity cycle and targeting STING could synergize with existing immune-checkpoint therapies. However, the role of STING in GC, especially in EBVaGC, and its correlation with programmed death-ligand 1 (PD-L1) remain largely unclear. Methods: We collected 78 cases of EBVaGCs and 210 cases of EBV-negative GC (EBVnGC) from a total of 1,443 cases of GC analyzed by EBV-encoded small RNA in situ hybridization. We investigated STING and PD-L1 expression and their concomitant prognostic value in EBVaGCs and EBVnGCs using tissue microarray and immunohistochemistry. The effects of STING and PD-L1 expression on the overall survival of patients with EBVaGC or EBVnGC were assessed by univariate and multivariate analysis. Results: We found that both STING and PD-L1 exhibited significantly higher expression in the EBVaGCs than that in the EBVnGCs. The expression of STING was positively correlated with that of PD-L1 in EBVaGCs. Simultaneous negative expression of STING and PD-L1, and positive expression of STING were independent prognostic risk factors for EBVaGC and EBVnGC, respectively. Conclusions This is the first prognostic retrospective study of STING and PD-L1 expression and the prognosis among EBVaGC and EBVnGC. The expression and prognostic value of STING and PD-L1 are different in the two types of GCs. STING and PD-L1 are promising prognostic biomarkers and therapeutic targets for EBVaGC and EBVnGC.

Objective:To investigate the therapeutic efficacy and potential mechanisms of integrin α vβ 3-targeted radionuclide therapy (TRT) in combination with anti-programmed cell death protein ligand 1 (PD-L1) immunotherapy. Methods:Integrin α vβ 3-targeted molecule Arg-Gly-Asp (RGD) was conjugated with Evans blue (EB) and then labeled with 177Lu to obtain 177Lu-EB-RGD. The radioactivity and radiochemical purity were determined. MicroSPECT imaging, biodistribution, and in vivo therapeutic efficacy were subsequently performed in MC38 murine colon cancer models. Volume of tumor and body mass of mice were observed to assess the therapeutic efficacy and safety ( n=9 in each group). Flow cytometry was used to evaluate therapy response of saline-treated (control, group A), 18.5 MBq 177Lu-EB-RGD-treated (group B), 10 mg/kg PD-L1 antibody-treated (group C), TRT combined with immunotherapy-treated (group D, 18.5 MBq 177Lu-EB-RGD and 10 mg/kg PD-L1 antibody) mice and alterations in tumor microenvironment (PD-L1 + immune cells, CD8 + T cells and regulatory T cells). Independent-sample t test and repeated measures analysis of variance were used for data analysis. Results:The radioactivity of 177Lu-EB-RGD was (55.85±14.00) GBq/μmol. SPECT imaging clearly visualized the MC38 tumors in mice models with high uptake and long retention time, the tumor/muscle ratio reached 14.87±0.88 at 24 h postinjection, while less uptake and retention in normal tissues. Tumor uptake of 177Lu-EB-RGD was significantly higher than that of 177Lu-RGD 4 h post-injection ((12.00±1.60) vs (3.69±0.37) %ID/g; t=8.63, P<0.01). The efficacy results between each treatment group was significantly different ( F=7.32, P=0.03) at day 6 post-treatment. The combination therapy showed the most outstanding anti-tumor efficacy with 7/9 mice showed complete response. Flow cytometry results showed that TRT up-regulated the PD-L1 expression significantly, namely, PD-L1 + immune cells in group B and group A were significantly different (CD45 + /PD-L1: 2.34% vs 0.95%, CD11b + /PD-L1: 2.41% vs 0.66%; t values: 11.17 and 8.70, both P<0.01); immunotherapy and combination therapy dramatically stimulated the infiltration of CD8 + T cells (2.07% vs 0.26%, 2.71% vs 0.26%; t values: 4.10 and 6.03, both P<0.05). Conclusion:TRT in combination with immunotherapy synergistically enhance anti-tumor efficacy, which is expected to play a role in the treatment of patients with advanced tumor where TRT can be applied.

Objective This study will compare crystalloid to colloid for goal-directed fluid therapy (GDFT) in cesarean section under combined spinal epidural anesthesia,and to discuss which type of fluid is more effective to prevent perioperative hypotention.Methods We randomly assigned 60 patients (ASA Ⅰ-Ⅱ) scheduled undergoing cesarean section into two groups:colloid group and crystalloid group.The colloid group received balanced 6％ HES (130/0.4,Volulyte) and Lactated Ringer's solution (LR),while the crystalloid group just received LR as haemodynamic optimization fluid.The primary outcomes included the incidence of maternal hypotension,and vasopressor doses prior to delivery.The secondary outcomes included umbilical blood gas abnormalities,neonatal Apgar grade and adverse events.Results The impact fluid volume,total liquid volume and urine volume in the crystalloid group were more than those in the colloid group (P ＜ 0.05).No statistical difference was seen in the number of patients who showed hypotension,vomiting and nausea between two groups.And there was no significant difference in the incidence of neonatal adverse effects between two groups.Conclusions No evidence showed that colloid had more advantages in GDFT for patients received cesarean section under combined spinal epidural anesthesia,except that the volume of colloid input was less than crystalloid.

Regional cerebral oxygenation(rSO2) is widely used in the monitoring of cerebral blood flow,which is not affected by temperature and pulsatile blood flow.rSO2monitoring gives us a new way to monitor the oxygenation status of brain regions.But,currently,rSO2research in the neonates is rare.This pa-per summarized the different pathological conditions influence on early neonatal rSO2,clarified the important clinical significance of monitoring of neonatal rSO2and the future application was prospected.

Objective To analyze the stress distributions under static loading and impact simulation in the process of tibial plateau fracture using finite element analysis,providing evidence for individualized diagnosis and treatment of tibial plateau fracture.Methods A healthy male volunteer was recruited.A 3D finite element model of a whole knee joint with ligaments,menisci and articular surfaces was generated using CT,MRI and 3D finite element software.The knee joint model was given the nature and parameters after reconstruction.According to the features of tibial plateau fracture,different operating conditions were designed.The stress distributions under static loading and impact simulation in the process of tibial plateau fracture were characterized by finite element analysis.Results Under static loads on the lateral condyle of the tibia,the stress was mainly concentrated on the front edge of the tibial plateau,especially the lateral stress.The stress on the medial condyle of the tibia was significantly increased,and the medial stress extended downwards to the tibial shaft.When the vertical stress moved towards outside,it extended from both sides of the internal and external condyles downwards to the tibia,and the value of lateral platform stress was slightly larger than that on the inside.In collisions,the stresses distributed on the neutral position were the same with the static loads.The stress on the medial condyle of the tibia was significantly increased,extending downwards the tibial shaft when it fell to the inside slope.When it fell to the outside slope,the stress on the tibial plateau was mainly distributed on most of the front edges of lateral and medial platforms,and the stress distributed on the fibula increased obviously.Conclusions The medial tibial plateau plays a major role in bearing stress loads.The stress is more concentrated on the lateral platform but distributed on a larger area of the medial platform,extending downwards the metaphysis.Therefore,small split fractures are likely to occur on the outer edge of the platform while fractures of a large fragment are likely to occur on the medial platform,even involving the metaphysis.